Despite advances in our understanding of AIDS and its etiologic agents, HIV-1 and HIV-2, there is no well-established animal model to study potential therapies and vaccines for HIV-induced diseases. Of the non-human primates, the chimpanzee (H. J. Alter, et al., Science, 226, 549-552 (1984); P. N. Fultz, et al., Journal of Virology, 58, 116-124 (1986)) and Macaca nemestrina (M. B. Agy, et al., Science, 257, 103-106 (1992)) are the major species susceptible to HIV-1 infection. Apart from some symptoms of acute infection observed in the macaque model, in neither of these systems have animals developed symptoms generally associated with immune system diseases (symptoms of AIDS). In the case of the chimpanzee, the ability to infect and cause disease, together with their endangered species status and cost, makes their use problematic. Moreover, most evidence indicates that reproducible persistent infection of M. nemestrina with HIV-1 strains cannot be achieved (L. R. Frumkin, et al., Virology 195, 422-431 (1993).
The most promising animal models presently being evaluated for studies of HIV pathogenesis and antiviral approaches are rhesus macaques infected with SIV.sub.mac strains (R. C. Desrosiers, Annual Review of Immunology 8, 557-558 (1990); M. B. Gardner, P. A. Luciw, Federation of American Societies for Experimental Biology Journal 3. 2593-2606 (1989)) and SIV.sub.mac /HIV-1 chimeras (J. Li, C. I. Lord, W. Haseltine, N. L. Letvin, J. Sodroski, Journal of Acquired Immune Deficiency Syndromes 5, 639-646 (1992); R. Shibata, A. Adachi, AIDS Research and Human Retroviruses 8, 403-409 (1992)). However, despite the close relatedness of certain SIV and HIV-2 strains, results obtained using these SIV-based models may not be directly applicable to infection with a human lentivirus.
It has also been shown that specific HIV strains will infect non-human primate PBMC. (See Castro, et al., Virology 184, 219-226 (1991)). Other models employing HIV-2 infection of various macaque species have also been studied (J. Livartowski, et al., Cancer-Detection and Prevention 16, 341-345 (1992); C. Stahl-Hennig, et al., AIDS 6, 611-617 (1990); P. Putkonen, et al., Journal of Acquired Immune Deficiency Syndromes 2, 366-373 (1989)), but the virus showed pathogenicity only after serial passage through M. nemestrina (J. McClure, et al., Abstract, 10th Annual Symposium on Nonhuman Primate Models for AIDS (1992)). Therefore, an important need exists for a reproducible and affordable animal model of viral persistence and pathogenesis which can employ various HIV strains to test possible vaccine and antiviral strategies. The present invention serves that need.